Effects of Carvedilol on Cardiotoxicity in Cancer Patients Submitted to Anthracycline Therapy (CardioTox)

Hospital Sirio-Libanes

Status and phase: Enrolling; Phase 4

Conditions: Cancer

Treatments: Drug: Placebo; Drug: Carvedilol

Study type: Interventional

Funder types: Other

Identifiers

NCT04939883

AVAP-NG 989

Details and patient eligibility

About

Neoplasia is the main cause of general death in the Brazilian population. In 2016, they were responsible for approximately 211,343 (16%) deaths, followed by cardiovascular diseases (12.6%). Despite the high mortality rate of neoplasia, oncological treatment have advanced substantially in recent decades improving the prognosis of patients. However, growing evidence suggest that some oncological agents may induce significant toxicity that may play a major role in the quality of life, morbidity and mortality. The cardiovascular system is often negatively affected with cancer therapy, predisposing several patients to stop appropriate treatments or to have cardiovascular events related to the cardiotoxicity. The most typical manifestation of cardiotoxicity and related consequences (heart failure) are related to the use of anthracyclines. Anthracyclines are part of the chemotherapy regimen for solid tumors and hematological neoplasms in children and adults, and are associated with an increase in life expectancy. Carvedilol is an α and β-blocker that also has antioxidant properties. Preliminary studies have shown that carvedilol and its metabolites prevent lipid peroxidation, inhibit the formation and inactivate free radicals, in addition to preventing the depletion of endogenous antioxidants, such as vitamin E. These effects would potentially prevent anthracycline injury but definitive evidence is still needed. This is a multi-center, double-blind, randomized, placebo-controlled study that aims to establish the efficacy of carvedilol for the primary prevention of left ventricular systolic dysfunction in cancer patients obtained with anthracycline chemotherapy, in different schedules and doses.

Enrollment: 1,018 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ≥18 years of age at the time of screening
• Cancer patients that will receive chemotherapy with anthracyclines.

Exclusion criteria

• Inability to adequate asses left ventricular function
• Previous symptoms (dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, and pulmonary and systemic congestion) suggestive of or a previous diagnosis of heart failure.
• Previous history of any cardiomyopathy (eg.: valve disease, Chagas' disease, infiltrative cardiomyopathy)
• LVEF < 50%
• Previous history of myocardial revascularization
• Permanent tachyarrhythmia (flutter, atrial fibrillation, atrial tachycardia)
• Congenital heart disease with left ventricular function impared
• Contra-indication to the use of beta-blockers.
• Pregnant or Breast-feeding females or women of childbearing age who intend to became pregnant.
• On kidney replacement therapy
• ECOG >= 4 or Karnofsky <=30
• Advanced hepatic failure (C score Child-Pugh and MELD > 15);
• Previous use of anthracycline
• Have any serious concomitant systemic disease, condition, or disorder that, in the opinion of the investigator, should preclude participation in this study
• Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,018 participants in 2 patient groups, including a placebo group

Intervention Group

Experimental group

Description:

Patients allocated to the intervention group will receive carvedilol 6.25 mg twice daily, then increased to 12.5 mg twice daily, until maximum dose of 25 mg twice daily according to the patients' tolerance; The dosis increments will occur every 5 days. If after the increment the patient develops bradycardia or hypotension, the dose will be reduced to the maximum tolerated dose. Carvedilol will ideally be maintained for up to 30 days after the end of chemotherapy.

Treatment:

Drug: Carvedilol

Control Group

Placebo Comparator group

Description:

Patients allocated to this group will receive placebo in a presumably staggered and progressive manner similar to the group intervention. The placebo will ideally be maintained for up to 30 days after the end of chemotherapy.

Treatment:

Drug: Placebo